Figure 2. Positive and negative regulation of MAVS-mediated antiviral signaling pathway. Upon viral infection, sensing of viral dsRNA by RLRs induces the formation of MAVS signalosome on mitochondria followed by promotion in downstream IFN synthesis. TNF receptor-associated factor 6 (TRAF6), TNFR1–associated death domain protein (TRADD), tripartite motif 14 (TRIM14) and pyruvate carboxylase (PC) modulates canonical NF-κB signaling pathway. Activated IκB kinase (IKK) complex (IKK α/β/γ) induces phosphorylation of NF–κB inhibitor–α (IκBα), resulting in NF–κB nuclear translocation and transcriptional activation of proinflammatory cytokines gene expression. MAVS also interacts with TRAF2/3, TANK, IKKe and TBK1. TBK1-mediated phosphorylation of IRF3 and IRF7 and subsequent their dimerization promotes type I IFN gene expression through nuclear translocation. Various molecules are involved in negative regulation of MAVS signaling. Poly(RC)-binding protein (PCBP) 1 and PCBP2 induces Lys48-linked polyubiquitination of MAVS, resulting in its proteasomal proteosomal degradation. Also, Smad ubiquitin regulatory factor 2 (Smurf2) binding to MAVS reduces antiviral type I IFN production through proteosomal degradation of MAVS. 20S proteasomal subunit PSMA7 negatively regulates MAVS signaling by promoting degradation, NLR family member X1 (NLRX1) downregulates type I IFN production by inhibiting between MAVS and RIG-I direct interaction. Cytochrome c oxidase (CcO) complex subunit (COX5B) downregulates type I IFN production by physical interaction with MAVS. UBX-domain-containing protein UBXN1 inhibit MAVS oligomerization, resulting in inhibition of antiviral signaling pathway.